11-89007211-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143831.3(GRM5):c.661+40001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,154 control chromosomes in the GnomAD database, including 48,564 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48564 hom., cov: 33)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM5	NM_001143831.3	c.661+40001T>C		intron_variant		ENST00000305447.5
GRM5	NM_000842.5	c.661+40001T>C		intron_variant
GRM5	NM_001384268.1	c.661+40001T>C		intron_variant
GRM5	XM_011542792.2	c.661+40001T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM5	ENST00000305447.5	c.661+40001T>C		intron_variant		1	NM_001143831.3	A2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120418 AN: 152036 Hom.: 48500 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120538 AN: 152154 Hom.: 48564 Cov.: 33 AF XY: 0.793 AC XY: 58950 AN XY: 74378

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.790

Alfa AF: 0.738 Hom.: 52054

Bravo AF: 0.802

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.54
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7120151; hg19: chr11-88740379;